The longitudinal monitoring for the myocardium

The imaging techniques , in suitable parameters , provide the connection between the cell therapies and the clinical procedure . The longitudinal monitoring provides information about the functioning mechanism of the reprogrammed cells in the in vivo environment . The review presents the imaging techniques that are able to explain the cause for the limited restoration process of the cell therapies in the cardiac tissue .

The human body contains approximately 3 , 7 × 10¹³ cells . The heart contains 6 × 10⁹ cells , in 300 grams ( figure 1 ) . The damage of the heart does not lead automatically to the regeneration of the full functional capacity . The scar formation and the inflammatory signals may not be enough to have a full regeneration of the cardiac tissue . The regenerative medicine enhances the healing mechanisms of the body with the cell therapy .

Figure 1 . The number of cells in the parts of the human body .
Copyright ( 2014 ) Katie Vicari / Nature Publishing Group

The minimum number of injected cells that is detectable by the imaging techniques is in the range of 10⁴ - 10⁶ cells . The heart contains 2 × 10⁷ cells in one gram of tissue , in the left ventricle . The fused positron emission tomography ( PET ) - computed tomography ( CT ) image of the porcine heart is an example for the technique ( figure 2 ) . The long arrows point to the trajectory of the thoracotomy . T is the inserted tube . The short arrows point to the 10⁸ human mesenchymal stem cells , injected in the left ventricle ( LV ) . The %ID / g is the percentage of the uptake by the injected human cells in one gram of porcine cardiac tissue .

Figure 2 . The PET - CT imaging of the expression for the reporter gene in the porcine myocardium .
Copyright ( 2009 ) RSNA

The results of a porcine model for the myocardial infarction identifies as the time for the maximum proliferation at an interval of 33 - 35 days after the injection of the mesenchymal stem cells in the myocardium .

The injected cells are not tracked in vivo if they are not labelled in vitro . The nanoparticles , as the exogeneous label , provide a strong contrast in a short acquisition time , but it is unreliable in the long - term monitoring . The incorporation process of reporter genes labels indirectly the target cell . The reporter gene in the nucleus creates reporter proteins secreted in the cytoplasm . The imaging technique detects the reporter proteins . The ideal cell label stays inside the target cells for a long time , is non - toxic , is in a concentration that is stoichiometric related to the number of target cells , and clears the system rapidly after the apoptosis of the target cells .

The challenges of the imaging techniques are the label dilution , and the cell tracking . The label dilution should remain inside the tracked cells until the apoptosis , but sometimes the dilution transfers to the host cells . The long - term tracking of the implanted cells through the imaging techniques has the challenge to quantify the number of cells from the initial implantation procedure that are alive , and the number of cells that proliferate , in the spatial and the temporal dimension .

The infarcted myocardium is trully regenerated with the aid from the cell therapies when the viable cardiac tissue in the infarct area has the volume increased , the fiber architecture is integer in structure , and the regenerated myocardium has synchronous contraction with the host .

References :

Naumova A . V . , Modo M . , Moore A . , Murry C . E . , Frank J . A . ( 2014 ) “ Clinical imaging in regenerative medicine ” , Nature Biotechnology , 32 ( 8 ) , 804 - 818 .

Willmann J . K . , Paulmurugan R . , Rodriguez - Porcel M . , Stein W . , Brinton T . J . , Connolly A . J . , Nielsen C . H . , Lutz A . M . , Lyons J . , Ikeno F . , Suzuki Y . , Rosenberg J . , Chen I . Y . , Wu J . C . , Yeung A . C . , Yock P . , Robbins R . C . , Gambhir S . S . ( 2009 ) “ Imaging gene expression in human mesenchymal stem cells : from small to large animals ” , Radiology - Radiological Society of North America , 252 ( 1 ) , 117 - 127 .

The effects on the heart after the replacement for the mitral valve

The echocardiographic investigation of the mitral valve shows which leaflet is degenerated , if the leaflet , and the ring , maintained the integrity , the state of the attachment for the chorda tendinae , the structure of the papillary muscles . Two follow - up studies present the outcome of the mitral valvuloplasty for the elderly patients .

A study presents the clinical findings for a man of 74 years old . He did not have regurgitation of the tricuspid valve before he had a prosthetic replacement for the mitral valve . The left side of the heart stabilised with the surgery . The aortic valve had an unaffected functioning mechanism . The postoperative atrial fibrillation progressed. The postoperative regurgitation of the tricuspid valve made an impact on the right side of the heart .

The rheumatic heart disease ( RHD ) , and the dilated cardiomyopathy ( DCM ) are the causes for the stenosis ( MS ) , and for the regurgitation ( MR ) of the mitral valve ( figure 1 ) . The effects of the increased pressure in the left atrium are the increased size of the left atrium , the atrial fibrillation , and the pulmonary hypertension . The atrial fibrillation produces the dilation for the ring of the tricuspid valve . The pulmonary hypertension generates the dilation of the right ventricle ( RV ) . The regurgitation of the tricuspid valve ( TV ) worsens the tethering of the tricuspid valve , and the dilation of the right ventricle .

Figure 1 . The regurgitation of the tricuspid valve after the mitral valvuloplasty . Copyright ( 2009 ) Journal of The American College of Cardiology .

Another follow - up study analyses the clinical outcome for 242 patients who had valvuloplasty for the repair of the mitral valve . The patients are free from the non - trivial regurgitation of the mitral valve in 94 . 3 ± 1 . 6 % after one month , 58 . 6 ± 4 . 9 % after five years , and 27 . 2 ± 8 . 6 % after seven years ( figure 2 ) . The freedom from the severe regurgitation of the mitral valve is 98 . 3 ± 0 . 9 % after one month , 82 . 8 ± 3 . 8 % after five years , and 71 . 1 ± 7 . 4 % after seven years .

Figure 2 . The non - trivial regurgitation of the mitral valve . Copyright ( 2003 ) Circulation .

The dysfunction of the mitral valve is generated by the rheumatic heart disease , by the ischemic heart disease , and by the bacterial endocarditis . The succes of the replacement for the mitral valve is assessed both in the short term , and in the long term effects on the quality of life for the patient .

References :

Flameng W . , Herijgers P . , Bogaers K . ( 2003 ) “ The clinical anatomy and pathology of the human arterial valves : implications for repair or replacement ” , Circulation , 107 , 1609 - 1613 .

Shiran A . , Sagie A . ( 2009 ) “ Tricuspid regurgitation in mitral valve disease : incidence , prognostic implications , mechanism , and management ” , Journal of The American College of Cardiology , 53 ( 5 ) , 401 - 408 .

Features of the pulmonary valve

The aortic and the pulmonary valves are anatomical structures of high complexity . The assessment , and the treatment methodology is developed for the disorders of the two semilunar , tricuspid valves . The proper functioning mechanism of the semilunar valve is represented by the closed phase during systole , and the open one during diastole ( figure 1 ) . The valve stenosis is generated by the inability of the valve to open successfully . The regurgitation of the blood is caused by the incapacitation of the valve to close shut .

Figure 1 . The internal videoscopic view of the pulmonary valve in the reanimated human heart , sagittal superior ( a , b ) , sagital inferior ( c , d ) , in systole ( a , c ) , in diastole ( b , d ) . Copyright ( 2013 ) Springer .

The three dimensional arrangement of the pulmonary valve is maintained by the histological structure designed with the fibrosa , the spongiosa , and The Nodulus Arantii ( figure 2 ) . The mean value for the annular diameter of the pulmonary valve is 25 . 4 ± 3 . 2 ( N = 3997 ) , and the mean value for the aortic valve is 22 . 4 ± 2 . 7 ( N = 3370 ) .

Figure 2 . The idealised three - dimensional structure of the semilunar valve . Copyright ( 2013 ) Journal of Cardiovascular Translational Research .

The surgery on the pulmonary valve presents less risk because the pressure gradient across the valve is low , comparing to the one for the aortic valve . Both the pulmonary and the aortic valve have similar dimensions , with slightly different material properties ( figure 3 ) . The pulmonary valve is considered as autograft replacement for the aortic valve in some patients with congenital heart disorders .

Figure 3 . The name of the leaflets for the semilunar valves . Copyright ( 2013 ) Springer .

Four of the 3861 hearts analysed by The European Homograft Bank have the pulmonary valve with two leaflets . Eight of the 109571 autopsies present an aneurysm of the pulmonary artery . A patient with both these conditions may have had an anomaly in the embryonic development .

References :

Batesman M . G . , Hill A . J . , Quill J . L . , Iaizzo P . A . ( 2013 ) “ The clinical anatomy and pathology of the human arterial valves : implications for repair or replacement ” , Journal of Cardiovascular Translational Research , 6 ( 2 ) , 166 - 175 .

Capps S . B . , Elkins R . C . , Fronk D . M . ( 2000 ) “ Body surface area as a predictor of aortic and pulmonary valve diameter ” , The Journal of Thoracic and Cardiovascular Surgery , 119 , 975 - 982 .

Iaizzo P . A . , Bianco R . W . , Hill A . J . , Louis J . D . S . ( 2013 ) “ Heart valves : from design to clinical implantation ” , Springer , part I . 2 , 27 - 45 .

The postoperative atrial fibrillation

The fast and irregular flow of the blood reduces the efficiency of the heart . The incidence of atrial fibrillation after cardiac surgery is 18.8 % of 49 264 patients , from the database between 2001 until 2012 in The Virginia Cardiac Surgery Quality Initiative . It is the cause of one in five strokes , and it reduces the quality of life . When it occurs after heart surgery , the risk of symptomatic hypotension , thromboembolism and heart failure is increased .

The European Society of Cardiology published guidelines for the control of the ventricular rate . There are five types of clinical symptoms for atrial fibrillation ( AF ), based on the time length : newly diagnosed , paroxysmal ( 2 days ) , persistent ( 7 days ) , long - standing persistent and permanent ( 1 year ) . The AF is associated with alterations of the extracellular matrix ( amyloid deposition , inflammatory behaviour , interstitial fibrosis ) , of the myocyte ( apoptosis , hypertrophy , intracellular accumulation of substrate ) , at microvascular level , and with remodelling of the endocardium .

Prolonged hospitalization may be required as the postoperative AF develops in the first three days after heart surgery . The systemic inflammation , triggered by the extracorporeal blood circulation during surgery , and the reactive oxygen species ( ROS ) in the atria are the causes for the postoperative AF .

Monoamine oxidase ( MAO ) is an enzyme on the outer membrane of the mithocondrion in the cardiac cell . It is a major factor in the balance between the reduction and the oxidation reactions in the atrial myocardium . The emission of mitochondrial H2O2 was measured in samples of myocardial tissue from 244 patients for cardiopulmonary bypass . Figure 1 outlines the incidence quartiles of postoperative AF in the cohort based on the enzymatic activity .

Figure 1 . The activity of the MAO and the incidence of the postoperative AF . Copyright ( 2014 ) Journal of The American Heart Association .

There are gaps in the clinical evidence that need to be understood :

Diagnosis

• the increase in the electrocardiogram ( ECG ) screening
• the benefit of multimodal therapy

Epidemiology

• effective biomarkers for antithrombotic therapy
• increase the cohort with undiagnosed AF

Rhythm control

• the atrioventricular node ablation

References :

Anderson E . J . , Efird J . T . , Davies S . W . , O ‘ Neal W . T . , Darden T . M . , Thayne K . A . , Katunga L . A . , Kindell L . C . , Ferguson B . , Anderson C . A . , Chitwood W . R . , Koutlas T . C . , Williams J . M . , Rodriguez E . , Kypson A . P . ( 2014 ) “ Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation ” , Journal of the American Heart Association , 3 .

Camm A . J . , Kirchhof P . , Lip G . Y . H . , Schotten U . , Savelieva I . , Ernst S . , Van Gelder I . C. , Al – Attar N . , Hindricks G . , Prendergast B . , Heidbuchel H . , Alfieri O . , Angelini A . , Atar D . , Colonna P . , De Caterina R . , De Sutter J . , Goette A . , Gorenek B . , Heldal M . , Hohloser S . H . , Kolh P . , Le Heuzey J . - Y . , Ponikowski P . , Rutten F . H . ( 2010 ) “ Guidelines for the management of atrial fibrillation ” , European Heart Journal , 31 , 2369 - 2429 .

LaPar D . J . , Speir A . M . , Crosby I . K . , Fonner E . , Brown M . , Rich J . B . , Quader M . , Kern J . A . , Kron I . L . , Ailawadi G . ( 2014 ) “ Postoperative atrial fibrillation significantly increases mortality , hospital readmission , and hospital costs ” , The Annals of Thoracic Surgery , 98 ( 2 ) , 527 – 533 .

Key advances in medicine 2014

Nature Reviews published in february 2014 this electronic book free for download on the website .

International experts identified key trends in clinical studies from 2013 . They published 45 articles in 8 medical specialities :

Cardiology

• acute coronary syndromes
• cardiovascular imaging
• dyslipidaemia
• heart failure
• venous thromboembolism

Clinical endocrinology

• adrenal cancer
• metabolism
• puberty
• steroid hormones
• thyroid cancer
• type 2 diabetes mellitus

Clinical oncology

• breast cancer
• cervical cancer
• colorectal cancer
• liver cancer
• lung cancer
• melanoma

Gastroenterology and hepatology

• acute kidney injury
• barrett oesophagus
• cardiovascular disease in chronic kidney disease
• coeliac disease
• faecal microbiota transplantation
• genetics in kidney disease
• hepatitis c
• inflammatory bowel disease
• small bowel endoscopy
• stem cells
• transplantation immunology

Neurology

• dementia
• epilepsy
• movement disorders
• multiple sclerosis
• neuro - oncology
• stroke

Rheumatology

• epigenetics
• gout
• imaging in rheumatology
• systemic lupus erythematosus
• rheumatoid arthritis

Urology

• bladder cancer
• female urology
• kidney cancer
• prostate cancer
• reconstruction
• testicular cancer

Each article has the citation information regarding the original publication . Fine reading !

The recovery heart rate time

It is time for vacation . An idea for doing science , while having a good time , is to study the recovery time of the heart rate . One may have the chance of being an athlete for a day .

The science project that I have in mind requires little effort from the volunteers . A few minutes are needed to fill in information regarding the physical activity . Then an e - mail is received with the location and time when the science project takes place . On the day of the event the person jogs on a park route for a few minutes . The heart rate is measured immediately after the exercise has finished , and after one and two minutes . The event is finished with refreshments .

From the technical point of view , the data is processed based on two equations :

• The maximum heart rate is 220 ( beats per minute ) minus percentage the age of the runner ;
• The target heart rate zone is 50 - 85 % of the maximum heart rate .

The variation with age and gender is analysed for both non - athletes and athletes .

Would you like to participate in this activity , then fill in the form .

The anesthetic for valvular regurgitation

The treatment plans are presented for both the aortic and the mitral valve . The acute and chronic phases are presented . The clinical findings for the functioning mechanism are presented through diagrams .The assessment of the functional capacity , the magnetic resonance images , the electrocardiography , the echo - measurements , and the physical examination are described for the preoperative phase . The presence of infective endocarditis is studied . The anesthetic management is outlined for the clinical environment .